Acid-stable polypeptides have been isolated from human tumor cells and from normal human tissues. These proteins are able to produce a reversible morphological transformation of normal rat kidney fibroblast cells that allows these cells to grow in a soft agar medium where normal cell growth is prevented. It is the purpose of this project to characterize these transforming growth factors and to ascertain the role these factors may play in the process of carcinogenesis. Initial investigation will concentrate on the purification and characterization of these polypeptides from normal human placenta as well as from HeLa and A673 (rhabdomyosarcoma) tumor cell lines using gel filtration, ion exchange and high pressure liquid chromatography. Once these proteins have been characterized, analogs will be synthesized and tested for their ability to inhibit the transforming activity of the natural peptide and therefore, possibly, inhibit the transforming activity of the natural peptide and therefore, possibly, inhibit the carcinogenic process itself. Finally, the mechanism whereby these factors interact with the cell to cause phenotypic cell transformation will be investigated in order to gain a greater understanding of the process of carcinogenesis.